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Study of ASKP1240 After a Single Intravenous Dose at Escalating Dose Levels in Healthy Subjects

This study has been completed.
Sponsor:
Collaborator:
Kyowa Hakko Kirin Company, Limited
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
ClinicalTrials.gov Identifier:
NCT01565681
First received: March 27, 2012
Last updated: December 7, 2012
Last verified: December 2012
  Purpose

The objective of this study is to evaluate the safety, tolerability, pharmacodynamics and pharmacokinetics of ASKP1240 after a single intravenous dose at escalating dose levels in healthy subjects.


Condition Intervention Phase
Pharmacokinetics of ASKP1240
Healthy Volunteers
Drug: ASP1240
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Official Title: A Phase 1 Single Ascending Dose Study of ASKP1240 in Healthy Male and Female Volunteers

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • Pharmacodynamic variable: Individual subject cell surface antigen (CD40) occupancy levels over time [ Time Frame: Days 1-3, 5, 8,15, 22, 29, 43, 60, 75, and 90 ] [ Designated as safety issue: No ]
    binding of ASKP1240-biotin to B cells

  • Pharmacokinetics profile: AUCinf and Cmax [ Time Frame: Days 1-8,15, 22, 29, 43 and 60 ] [ Designated as safety issue: No ]
    Area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUCinf) and Maximum concentration of study drug (Cmax)


Secondary Outcome Measures:
  • Pharmacokinetics profile: AUClast, tmax, t1/2, Vz, and CLtot [ Time Frame: Days 1-8,15, 22, 29, 43 and 60 ] [ Designated as safety issue: No ]
    Area under the plasma concentration-time curve from time 0 up to the last quantifiable concentration (AUClast),Time to attain Cmax (tmax), Apparent terminal elimination of half-life (t1/2), Apparent volume of distribution ( Vz), and Total body clearance (CLtot)

  • Total lymphocyte count [ Time Frame: Day -1, Days 1-3, 5, 8,15, 22, 29, 43, and 60 ] [ Designated as safety issue: No ]
    product of the white blood count (WBC) and percent lymphocytes [from differential]

  • Peripheral lymphocyte subset quantification [ Time Frame: Day -1, Days 1-3, 5, 8,15, 22, 29, 43, and 60 ] [ Designated as safety issue: No ]
    leukocycte phenotypes: CD3, CD4, CD8,CD16, and CD20

  • Safety assessed by recording adverse events, laboratory assessments, vital signs, electrocardiograms (ECGs), physical examination, pulse oximetry, and incidence of anti-ASKP1240 antibody formation [ Time Frame: Up to day 90 ] [ Designated as safety issue: Yes ]

Enrollment: 109
Study Start Date: January 2009
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A: ASKP1240 lowest dose Drug: ASP1240
infusion
Experimental: Arm B: ASKP1240 second lowest dose Drug: ASP1240
infusion
Experimental: Arm C: ASKP1240 third lowest dose Drug: ASP1240
infusion
Experimental: Arm D: ASKP1240 fourth lowest dose Drug: ASP1240
infusion
Experimental: Arm E: ASKP1240 fifth lowest dose Drug: ASP1240
infusion
Experimental: Arm F: ASKP1240 middle dose Drug: ASP1240
infusion
Experimental: Arm G: ASKP1240 sixth highest dose Drug: ASP1240
infusion
Experimental: Arm H: ASKP1240 fifth highest dose Drug: ASP1240
infusion
Experimental: Arm I: ASKP1240 fourth highest dose Drug: ASP1240
infusion
Experimental: Arm J: ASKP1240 third highest dose Drug: ASP1240
infusion
Experimental: Arm K: ASKP1240 second highest dose Drug: ASP1240
infusion
Experimental: Arm L: ASKP1240 highest dose Drug: ASP1240
infusion
Placebo Comparator: Arm M: Placebo
Sodium Chloride solution
Drug: Placebo
infusion
Other Name: Sodium Chloride solution

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • The subject weighs at least 50 kg, and has a body mass index (BMI) of 18 to 32 kg/m2 inclusive
  • The female subject must be of non-childbearing potential (surgically sterile [hysterectomy or bilateral tubal ligation] or post-menopausal ≥ 1 year with follicle stimulating hormone [FSH] > 40 U/L)
  • Male subject agrees to no sperm donation until end of study or 90 days post dose, whichever is longer
  • The subject is highly likely to comply with the protocol and complete the study
  • The subject has a negative urine screen for drugs of abuse, and negative blood or breathalyzer alcohol screen at Screening and clinic admission on Day 1

Exclusion Criteria:

  • The subject has a history of severe allergic or anaphylactic reactions
  • The subject has history of consuming more than 14 units of alcoholic beverages per week or has a history of alcoholism or drug/chemical/substance abuse within past 2 years prior to screening (Note: one unit = 12 ounces of beer, 4 ounces of wine or 1 ounce of spirits)
  • The subject has/had a symptomatic, viral, bacterial (including upper respiratory infection), or fungal (non-cutaneous) infection within 1 week prior to clinic check in
  • The subject has a supine mean systolic blood pressure < 90 or > 160 mmHg and a mean diastolic blood pressure < 50 or > 90 mmHg, or pulse rate higher than 100 beats per min (bpm), either at screening or clinic check in (blood pressure measurements taken in triplicate after subject has been resting in a supine position for a minimum of 5 minutes)
  • The subject is known positive for human immunodeficiency virus (HIV) antibody
  • The subject has a positive test for hepatitis C antibody, or for hepatitis B virus surface antigen (HBsAg)
  • The subject has at screening or clinic check in that:

    1. white blood cell count (WBC) is < 3.5 or > upper limit of normal
    2. absolute neutrophil count (ANC) is <1.5 or > upper limit of normal
    3. platelet count (PLT) is outside the normal limit
    4. serum creatinine, total bilirubin, alanine aminotransferase (ALT), or aspartate aminotransferase (AST) are > upper limit of normal
    5. creatine phosphokinase (CPK) is > two times upper limit of normal
    6. international normalized ratio (INR) is > upper limit of normal
    7. OR remaining laboratory tests are outside the normal limits and considered by the investigator to be clinically significant with regard to the remaining per protocol laboratory tests
  • The subject has received a vaccine within 60 days prior to study drug administration
  • The subject has received any systemic immunosuppressant agent within 6 months prior to study drug administration.
  • The subject has received any antibody or biologic product within 6 months prior to study drug administration
  • The subject has received any systemic steroid within 2 months prior to study drug administration
  • The subject has had treatment with prescription or non-prescription drugs, including complementary and alternative medicines (CAM) and excluding over-the-counter (OTC) allergy medications, nasal steroids, nasal inhalers, oral contraceptives, stable hormone replacement therapy (HRT; per Investigator judgment and dose change not expected during study), and intermittent acetaminophen, within 14 days prior to study drug administration
  • The subject has received an experimental agent within 30 days or ten half-lives, whichever is longer, prior to study drug administration
  • The subject is participating in another clinical trial or has participated in another dose group of the current trial
  • The subject has donated or has had significant blood loss or received a transfusion of any blood or blood products within 60 days or donated plasma within 7 days prior to dosing
  • The subject has a history of heavy smoking or has used tobacco-containing products and nicotine or nicotine-containing products in the past six months prior to Screening
  • The subject has a history of thromboembolic or vascular disease especially deep vein thrombosis, pulmonary embolism and varices
  • The subject has a positive test for tuberculosis
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01565681

Locations
United States, Maryland
Parexel
Baltimore, Maryland, United States, 21225
Sponsors and Collaborators
Astellas Pharma Global Development, Inc.
Kyowa Hakko Kirin Company, Limited
Investigators
Study Director: Medical Director Astellas Pharma Global Development
  More Information

No publications provided

Responsible Party: Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
ClinicalTrials.gov Identifier: NCT01565681     History of Changes
Other Study ID Numbers: 7163-CL-0101
Study First Received: March 27, 2012
Last Updated: December 7, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Astellas Pharma Inc:
Healthy Volunteers
B cell CD40 receptor occupancy
anti-CD40 monoclonal antibody

ClinicalTrials.gov processed this record on November 25, 2014